Isolation, Structure Elucidation, and Synergistic Antibacterial Activity of a Novel Two-Component Lantibiotic Lichenicidin from Bacillus licheniformis VK21
Isolation, Structure Elucidation, and Synergistic Antibacterial Activity of a Novel Two-Component Lantibiotic Lichenicidin from Bacillus licheniformis VK21
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DOI：
10.1021/bi100871b
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发表时间：
2010-08-03
期刊：
影响因子：
2.9
通讯作者：
Ovchinnikova, Tatiana V.
中科院分区：
文献类型：
--
作者：
Shenkarev, Zakhar O.;Finkina, Ekaterina I.;Ovchinnikova, Tatiana V.
从生产菌株地衣芽孢杆菌 VK21 中分离出一种新型协同羊毛硫抗生素对，Lch α (3249.51 Da) 和 Lch beta (3019.36 Da)，称为地衣素 VK21。确定了 Lch α 和 Lch β 的化学和空间结构。每个肽含有 31 个氨基酸残基，通过 4 个分子内硫醚桥和 N 端 2-氧代丁酰基连接。通过甲醇溶液中的核磁共振波谱研究了 Lch α 和 Lch β 的空间结构。 Lch α肽与美西丁样抗生素表现出结构同源性，并涉及结构相对良好的N端和C端结构域，这些结构域通过由硫醚桥Ala11-S-Ala21稳定的柔性环连接。相比之下，Lch β 肽代表延长的疏水性 α 螺旋，两侧具有更灵活的 N 端和 C 端结构域。对地衣芽孢杆菌 VK2 I 基因组的羊毛硫抗生素簇进行扩增和测序，该簇包含编码羊毛硫抗生素前体的结构基因 lchA1 和 /c/m12，以及修饰酶 IchMI 的基因。成熟肽 Lch α 和 Lch β 协同相互作用，在纳摩尔浓度范围内具有针对革兰氏阳性菌的抗生素活性，尽管单个肽在微摩尔浓度下显示出活性。我们的结果为了解地衣素 VK21 作用机制提供了分子视角。
A novel synergetic lantibiotic pair, Lch alpha (3249.51 Da) and Lch beta (3019.36 Da), termed lichenicidin VK21, was isolated from the producer strain Bacillus licheniformis VK21. Chemical and spatial structures of Lch alpha and Lch beta were determined. Each peptide contains 31 amino acid residues linked by 4 intramolecular thioether bridges and the N-terminal 2-oxobutyryl group. Spatial structures of Lch alpha and Lch beta were studied by NMR spectroscopy in methanol solution. The Lch alpha peptide displays structural homology with mersacidin-like !antibiotics and involves relatively well-structured N- and C-terminal domains connected by a flexible loop stabilized by a thioether bridge Ala11-S-Ala21. In contrast, the Lch beta peptide represents a prolonged hydrophobic a-helix flanked with more flexible N- and C-terminal domains. A lantibiotic cluster of the Bacillus licheniformis VK2 I genome which comprises the structural genes, lchA1 and /c/m12, encoding the lantibiotics precursors, as well as the gene of a modifying enzyme IchMI, was amplified and sequenced. The mature peptides, Lch alpha and Lch beta, interact synergistically to possess antibiotic activity against Gram-positive bacteria within a nanomolar concentration range, though the individual peptides were shown to be active at micromolar concentrations. Our results afford molecular insight into the mechanism of lichenicidin VK21 action.